ORGANIC
LETTERS
2
011
Vol. 13, No. 5
254–1257
Enantioselective Hydrocyanation of
Aldehydes Catalyzed by
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[Li{Ru(phgly) (binap)}]X (X = Cl, Br)
2
†
Nobuhito Kurono, Tatsuya Yoshikawa, Mikio Yamasaki, and Takeshi Ohkuma*
†
‡
,†
Division of Chemical Process Engineering, Faculty of Engineering, Hokkaido
University, Sapporo, Hokkaido 060-8628, Japan, and Rigaku Corporation,
Matsubara-cho, Akishima, Tokyo 196-8666, Japan
Received January 21, 2011
ABSTRACT
Novel bimetallic complexes [Li{Ru[(S)-phgly] [(S)-binap]}]X (X = Cl, Br) are readily synthesized by mixing Ru[(S)-phgly] [(S)-binap] and LiX. A
2
2
single-crystal X-ray analysis reveals the structure. These bimetallic complexes efficiently catalyze asymmetric hydrocyanation of aldehydes with
a substrate-to-catalyst molar ratio of 500-2000 at -78 to -60 °C. A range of aromatic, heteroaromatic, and R,β-unsaturated aldehydes as well as
a tert-alkyl aldehyde is converted to the cyanohydrins in high enantiomeric excess (up to 99%).
Enantioselective hydrocyanation of aldehydes is one of
the most direct and efficient methods to produce optically
by oxynitrilase has been used for the practical synthesis of
3
,4
such compounds. On the other hand, investigations of
artificial catalysts for this reaction have been limited. The
cyclic dipeptide cyclo-[(S)-phenylalanyl-(S)-histidyl] reported
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active cyanohydrins, which are useful intermediates for
the synthesisofbiologically importantcompounds, includ-
5-7
ing β-amino alcohols and R-hydroxy carboxylic acid
derivatives. This asymmetric transformation catalyzed
by Inoue and co-workers is an exception. Benzaldehyde
and HCN react with the dipeptide catalyst at a substrate-
to-catalyst molar ratio (S/C) of 50 to give mandelonitrile in
2
,3
†
Hokkaido University.
97% yield and 97% ee. A Ti(IV) complex with a modified
‡
Rigaku Corporation.
1) Reviews on optically active cyanohydrin chemistry: (a) North, M.
(
Synlett 1993, 807–820. (b) Effenberger, F. Angew. Chem., Int. Ed. Engl.
(4) Reviews on asymmetric synthesis catalyzed by oxynitrilases: (a)
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994, 33, 1555–1564. (c) Gregory, R. J. H. Chem. Rev. 1999, 99, 3649–
Griengl, H.; Schwab, H.; Fechter, M. Trends Biotechnol. 2000, 18, 252–
256. (b) Sharma, M.; Sharma, N. N.; Bhalla, T. C. Enzyme Microb.
Technol. 2005, 37, 279–294.
3682. (d) North, M. Tetrahedron: Asymmetry 2003, 14, 147–176.
(2) Reviews on chemical asymmetric synthesis of cyanohydrins: (a)
Mori, A.; Inoue, S. In Comprehensive Asymmetric Catalysis; Jacobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer, Berlin, 1999; Vol. 2, pp
(5) (a) Oku, J.; Inoue, S. J. Chem. Soc., Chem. Commun 1981, 229–
230. (b) Tanaka, K.; Mori, A.; Inoue, S. J. Org. Chem. 1990, 55, 181–185.
See also:(c) Jackson, W. R.; Jayatilake, G. S.; Matthews, B. R.; Wilshire,
C. Aust. J. Chem. 1988, 41, 203–213. (d) Danda, H. Synlett 1991, 263–
264. (e) Danda, H.; Nishikawa, H.; Otaka, K. J. Org. Chem. 1991, 56,
6740–6741.
(6) For mechanistic studies, see: (a) North, M. Tetrahedron 1992, 48,
5509–5522. (b) Shvo, Y.; Gal, M.; Becker, Y.; Elgavi, A. Tetrahedron:
Asymmetry 1996, 7, 911–924. (c) Kogut, E. F.; Thoen, J. C.; Lipton,
M. A. J. Org. Chem. 1998, 63, 4604–4610. (d) Schoenebeck, F.; Houk,
K. N. J. Org. Chem. 2009, 74, 1464–1472.
983-994. (b) Brunel, J.-M.; Holmes, I. P. Angew. Chem., Int. Ed. 2004,
43, 2752–2778. (c) Chem, F.-X.; Feng, X. Curr. Org. Synth. 2006, 3, 77–
97. (d) North, M.; Usanov, D. L.; Young, C. Chem. Rev. 2008, 108,
5146–5226. (e) Wang, W.; Liu, X.; Lin, L.; Feng, X. Eur. J. Org. Chem.
2010, 4751–4769. (f) Bergin, E. In Science of Synthesis: Stereoselective
Synthesis 2; Molander, G. A., Ed.; Thieme: Stuttgart, 2010; pp 531-583.
3) Reviews on enzymatic asymmetric synthesis of cyanohydrins: (a)
(
Gr o€ ger, H. Adv. Synth. Catal. 2001, 343, 547–558. (b) Poechlauer, P.;
Skranc., W.; Wubbolts, M. In Asymmetric Catalysis on Industrial Scale;
Blaser, H. U., Schmidt, E., Eds.; Wiley-VCH, Weinheim, Germany,
(7) For asymmetric reactions catalyzed by synthetic peptides, see:
Davie, E. A. C.; Mennen, S. M.; Xu, Y.; Miller, S. J. Chem. Rev. 2007,
107, 5759–5812.
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004; pp 151-164. (c) Garcia-Urdiales, E.; Alfonso, I.; Gotor, V. Chem.
Rev. 2005, 105, 313–354.
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0.1021/ol200187d r 2011 American Chemical Society
Published on Web 02/04/2011